Determinants of the accuracy of rapid diagnostic tests in malaria case management: evidence from low and moderate transmission settings in the East African highlands

BACKGROUND: The accuracy of malaria diagnosis has received renewed interest in recent years due to changes in treatment policies in favour of relatively high-cost artemisinin-based combination therapies. The use of rapid diagnostic tests (RDTs) based on histidine-rich protein 2 (HRP2) synthesized by Plasmodium falciparum has been widely advocated to save costs and to minimize inappropriate treatment of non-malarial febrile illnesses. HRP2-based RDTs are highly sensitive and stable; however, their specificity is a cause for concern, particularly in areas of intense malaria transmission due to persistence of HRP2 antigens from previous infections. METHODS: In this study, 78,454 clinically diagnosed malaria patients were tested using HRP2-based RDTs over a period of approximately four years in four highland sites in Kenya and Uganda representing hypoendemic to mesoendemic settings. In addition, the utility of the tests was evaluated in comparison with expert microscopy for disease management in 2,241 subjects in two sites with different endemicity levels over four months. RESULTS: RDT positivity rates varied by season and year, indicating temporal changes in accuracy of clinical diagnosis. Compared to expert microscopy, the sensitivity, specificity, positive predictive value and negative predictive value of the RDTs in a hypoendemic site were 90.0%, 99.9%, 90.0% and 99.9%, respectively. Corresponding measures at a mesoendemic site were 91.0%, 65.0%, 71.6% and 88.1%. Although sensitivities at the two sites were broadly comparable, levels of specificity varied considerably between the sites as well as according to month of test, age of patient, and presence or absence of fever during consultation. Specificity was relatively high in older age groups and increased towards the end of the transmission season, indicating the role played by anti-HRP2 antibodies. Patients with high parasite densities were more likely to test positive with RDTs than those with low density infections. CONCLUSION: RDTs may be effective when used in low endemicity situations, but high false positive error rates may occur in areas with moderately high transmission. Reports on specificity of RDTs and cost-effectiveness analyses on their use should be interpreted with caution as there may be wide variations in these measurements depending upon endemicity, season and the age group of patients studied

Costs of early detection systems for epidemic malaria in highland areas of Kenya and Uganda

BACKGROUND: Malaria epidemics cause substantial morbidity and mortality in highland areas of Africa. The costs of detecting and controlling these epidemics have not been explored adequately in the past. This study presents the costs of establishing and running an early detection system (EDS) for epidemic malaria in four districts in the highlands of Kenya and Uganda. METHODS: An economic costing was carried out from the health service provider's perspective in both countries. Staff time for data entry and processing, as well as supervising and coordinating EDS activities at district and national levels was recorded and associated opportunity costs estimated. A threshold analysis was carried out to determine the number of DALYs or deaths that would need to be averted in order for the EDS to be considered cost-effective. RESULTS: The total costs of the EDS per district per year ranged between US$ 14,439 and 15,512. Salaries were identified as major cost-drivers, although their relative contribution to overall costs varied by country. Costs of relaying surveillance data between facilities and district offices (typically by hand) were also substantial. Data from Uganda indicated that 4% or more of overall costs could potentially be saved by switching to data transfer via mobile phones. Based on commonly used thresholds, 96 DALYs in Uganda and 103 DALYs in Kenya would need to be averted annually in each district for the EDS to be considered cost-effective. CONCLUSION: Results from this analysis suggest that EDS are likely to be cost-effective. Further studies that include the costs and effects of the health systems' reaction prompted by EDS will need to be undertaken in order to obtain comprehensive cost-effectiveness estimates

Variations in entomological indices in relation to weather patterns and malaria incidence in East African highlands: implications for epidemic prevention and control

<p>Abstract</p> <p>Background</p> <p>Malaria epidemics remain a significant public health issue in the East African highlands. The aim of this study was to monitor temporal variations in vector densities in relation to changes in meteorological factors and malaria incidence at four highland sites in Kenya and Uganda and to evaluate the implications of these relationships for epidemic prediction and control.</p> <p>Methods</p> <p>Mosquitoes were collected weekly over a period of 47 months while meteorological variables and morbidity data were monitored concurrently. Mixed-effects Poisson regression was used to study the temporal associations of meteorological variables to vector densities and of the latter to incidence rates of <it>Plasmodium falciparum</it>.</p> <p>Results</p> <p><it>Anopheles gambiae </it>s.s. was the predominant vector followed by <it>Anopheles arabiensis</it>. <it>Anopheles funestus </it>was also found in low densities. Vector densities remained low even during periods of malaria outbreaks. Average temperature in previous month and rainfall in previous two months had a quadratic and linear relationship with <it>An. gambiae </it>s.s. density, respectively. A significant statistical interaction was also observed between average temperature and rainfall in the previous month. Increases in densities of this vector in previous two months showed a linear relationship with increased malaria incidence.</p> <p>Conclusion</p> <p>Although epidemics in highlands often appear to follow abnormal weather patterns, interactions between meteorological, entomological and morbidity variables are complex and need to be modelled mathematically to better elucidate the system. This study showed that routine entomological surveillance is not feasible for epidemic monitoring or prediction in areas with low endemicity. However, information on unusual increases in temperature and rainfall should be used to initiate rapid vector surveys to assess transmission risk.</p

District-based malaria epidemic early warning systems in East Africa: perceptions of acceptability and usefulness among key staff at health facility, district and central levels.

Malaria epidemics represent a significant public health problem in the highlands of Africa. Many of these epidemics occur in low resource settings, where the development of an effective system for malaria surveillance has been a key challenge. Between 2001 and 2006, the Highland Malaria Project (HIMAL) established a programme to develop and test a district-based surveillance system for the early detection and control of malaria epidemics in four pilot districts in Kenya and Uganda. An innovative feature of the programme was the devolution of responsibility for the detection of epidemics from the central Ministry of Health to District Health Management Teams. The implementation of the programme offered the opportunity to test both the technical aspects of the system and to examine the practical issues relating to the operation of the programme in the context of the existing health system. To investigate the attitude of key staff towards the programme, and their perceptions of its impact on their working practices, interviews were carried out among 52 health staff at district level and in the Ministries of Health in Kenya and Uganda. The transfer of responsibility for the early detection of epidemics to the districts had resulted in perceptions of individual empowerment among district-based staff. This, together with improved support supervision, was a key factor in sustaining motivation and improved surveillance. The enhanced support supervision also produced capacity benefits that extended beyond improved malaria surveillance. However, these improvements occurred in the context of increased logistical support (the provision of transport, fuel and travel allowances) which the participants believed was essential to the functioning of an effective system. With this proviso, the district-based malaria early warning system was perceived to be manageable, effective and sustainable in the context of the current health system

District-based malaria epidemic early warning systems in East Africa: Perceptions of acceptability and usefulness among key staff at health facility, district and central levels

Malaria epidemics represent a significant public health problem in the highlands of Africa. Many of these epidemics occur in low resource settings, where the development of an effective system for malaria surveillance has been a key challenge. Between 2001 and 2006, the Highland Malaria Project (HIMAL) established a programme to develop and test a district-based surveillance system for the early detection and control of malaria epidemics in four pilot districts in Kenya and Uganda. An innovative feature of the programme was the devolution of responsibility for the detection of epidemics from the central Ministry of Health to District Health Management Teams. The implementation of the programme offered the opportunity to test both the technical aspects of the system and to examine the practical issues relating to the operation of the programme in the context of the existing health system. To investigate the attitude of key staff towards the programme, and their perceptions of its impact on their working practices, interviews were carried out among 52 health staff at district level and in the Ministries of Health in Kenya and Uganda. The transfer of responsibility for the early detection of epidemics to the districts had resulted in perceptions of individual empowerment among district-based staff. This, together with improved support supervision, was a key factor in sustaining motivation and improved surveillance. The enhanced support supervision also produced capacity benefits that extended beyond improved malaria surveillance. However, these improvements occurred in the context of increased logistical support (the provision of transport, fuel and travel allowances) which the participants believed was essential to the functioning of an effective system. With this proviso, the district-based malaria early warning system was perceived to be manageable, effective and sustainable in the context of the current health system.East Africa Kenya Uganda Malaria epidemics Malaria early warning systems (MEWS) Surveillance Health worker perceptions Staff motivation